The stress-sensing domain of activated IRE1α forms helical filaments in narrow ER membrane tubes.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
21
10
2021
Statut:
ppublish
Résumé
The signaling network of the unfolded protein response (UPR) adjusts the protein-folding capacity of the endoplasmic reticulum (ER) according to need. The most conserved UPR sensor, IRE1α, spans the ER membrane and activates through oligomerization. IRE1α oligomers accumulate in dynamic foci. We determined the in situ structure of IRE1α foci by cryogenic correlated light and electron microscopy combined with electron cryo-tomography and complementary immuno–electron microscopy in mammalian cell lines. IRE1α foci localized to a network of narrow anastomosing ER tubes (diameter, ~28 nm) with complex branching. The lumen of the tubes contained protein filaments, which were likely composed of arrays of IRE1α lumenal domain dimers that were arranged in two intertwined, left-handed helices. This specialized ER subdomain may play a role in modulating IRE1α signaling.
Identifiants
pubmed: 34591618
doi: 10.1126/science.abh2474
pmc: PMC9041316
mid: NIHMS1797025
doi:
Substances chimiques
ERN1 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Endoribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
52-57Subventions
Organisme : NIAID NIH HHS
ID : P50 AI150464
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM032384
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122588
Pays : United States
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